The underlying assumption in the discussion of these concepts is that the drug of interest follows linear phar-macokinetic principles; that is, the concentrations achieved are proportional to the dose given. For example, a doubling of the dose will produce a doubling of the blood concentration. For some drugs, however, this is not the case: an increase in dose may produce a concentration much greater than expected. For example, increases in dosage of the antiepileptic agent phenytoin above approximately 300 mg daily usually produce a
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